title: Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues.
abstract: Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenotype and was not found in 374 population-matched alleles. The affected cysteine is highly conserved across vertebrates and its mutation is predicted to abolish a disulfide bond that defines the tertiary structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in development of the central nervous system and various connective tissues.
authors.affiliation: Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Saeed
authors.initials: S
authors.lastname: Bohlega
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Huda
authors.initials: H
authors.lastname: Al-Ajlan
authors.affiliation: 1] Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia [2] Laboratory of Neurogenetics, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Amr
authors.initials: A
authors.lastname: Al-Saif
mesh_terms: D019943:Amino Acid Substitution; D001921:Brain / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D002493:Central Nervous System Diseases / Q000235:genetics*; D002675:Child, Preschool; D002874:Chromosome Mapping; D003240:Connective Tissue Diseases / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D011487:Protein Conformation; D013116:Spinal Cord / Q000473:pathology; D013577:Syndrome
chemical_list: D002135:Calcium-Binding Proteins; C060820:fibulin